Understanding the basis of addiction requires insights at every level of neuroscience from defining the initial drug responses, the adaptive changes in cellular function resulting from drug exposure, the learning and memory plasticity changes at the neural circuit level encoding changes in motivation, the neuroeconomic calculations underlying aberrant choice, and the neuropathological changes resulting in co-morbid psychiatric disease. The ultimate goal of these studies is to identify new targets of intervention that can protect individuals from addiction, prevent the relapse of existing addiction behaviors, predict an individual's addiction risk, and thus reduce the huge personal, familial and societal costs of addiction. The next generation of scientists approaching the problem of addiction will use increasingly integrative approaches that actively combine molecular, genetic, and behavioral techniques to develop an understanding of how an addicted person's brain functions differently from non-addicted persons. Genetic tools to define drug addiction risk and proteomic tools to define functional changes in signaling complexes will play important roles. The University of Washington has research strength in many aspects of neuroscience, genome sciences, and psychiatry that comprise an outstanding and collaborative research environment. Some of the existing faculty have developed strong programs in drug-abuse research that build on this rich environment. However, we have important programmatic gaps that this proposed recruitment would help us address. Specifically, the university has made major investments during the last 15 years in genome sciences and proteomic research that have not yet been integrated into our equally strong investments in addiction research. The time is right to bridge this gap by recruiting someone interested in using the emerging tools of functional proteomics to better define the structural and functional changes distinguishing an addicted from normal brain. Identification of these key signaling structures and the processes responsible for their changes in the addicted state would hopefully provide new targets for rational therapeutic intervention. PUBLIC HEALTH RELEVANCE: Consistent with the aims of this ARRA Stimulus initiative, the University of Washington, School of Medicine proposes to recruit a tenure-track assistant professor in the area of drug abuse research. The newly hired individual would complement an existing group of NlDA-funded investigators having strengths in molecular pharmacology, targeted genetics, signal transduction and behavioral pharmacological approaches. We are seeking an individual using emerging proteomic or molecular genomic approaches to address questions of addictive drug actions on the structure and function of signaling complexes in brain.